The following relates to the development of a laser-induced fluorescence imaging endoscope for mapping cancerous or precancerous tissues in hollow organs. In initial clinical studies, on colon polyps, Ultraviolet (UV) lights was used at 370 nm to excite visible fluorescence (400-700 nm), the spectral signatures of which enabled differentiating between normal and abnormal tissues. Previously endoscopic imaging has been achieved using an optics module mounted in one of the biopsy ports of a two-port standard (white light) colonoscope. The optics module employs a quartz optical fiber and associated optics to deliver the UV light to the tissue, and a coherent quartz fiber-optic bundle to transmit the resulting fluorescence image to the proximal side of the endoscope, where a filter removes the large background of reflected UV light and the fluorescence image is then captured by a high-gain CCD detector array.
Endoscopically-collected autofluorescence images of colonic mucosa can be used as a screening tool for detecting pre-cursors to colorectal cancer (CRC). Fluorescence has been used to distinguish between normal mucosa and adenomas. In particular, spectra measured with single point contact probes with the use of several different excitation wavelengths.
Fluorescence spectra have been obtained through optical fiber probes with several excitation wavelengths. An in vitro study performed a search over a wide range of excitation wavelengths, and concluded that 370 nm is optimal for distinguishing between normal mucosa and adenoma. Both in vitro and in vivo studies using adenomatous polyps as a model for dysplasia have shown that with this wavelength dysplasia has less peak intensity at 460 nm and may have increased fluorescence at 680 nm compared with normal colonic mucosa. Furthermore, the morphologic basis for these spectral differences have been studied by fluorescence microscopy. The decreased fluorescence intensity in polyps was attributed to its raised architecture, increased vasculature, and reduced collagen in the lamina propria. The red enhancements arise from increased fluorescence of the crypt cells, which may be caused by higher levels of porphyrin.
The present invention relates to imaging endoscopes and in particular to a fluorescence imaging colonoscope using a dual channel electronic endoscope that employs a charge coupled device (CCD) chip or other solid state imaging device mounted on its distal tip to collect the white light image. Of particular significance for the present invention is that this chip can also collect the fluorescence image, displaying it on the endoscope""s video monitor with much larger signal size than that obtained using the optics module and intensified CCD camera. This configuration was used to collect fluorescence images of colonic dysplasia. Video images of two small FAP polyps, have been taken with the standard white light image and the unprocessed fluorescence image.
The CCD detector, which lacks gain intensification, detects the weak fluorescence signals, which are six orders of magnitude smaller in intensity than the diffusely reflected white light image. In addition, it is surprising that reflected 370 nm excitation light did not completely flood the CCD, obscuring the fluorescence signal. This results from the fact that the CCD spectral response falls off to zero quickly at wavelengths below 400 nm. Thus, the CCD effectively serves as its own long pass filter. Other imaging devices can be used with a filter to reduce by at least one half the detected intensity in the ultraviolet region relative to the detected intensity in the visible region.
In this particular embodiment, the CCD has a resolution of 270xc3x97328 pixels and an objective lens of 2.5 mm in diameter. The images are collected in 33 ms in RGB format. The advantages of this particular embodiment include that the in vitro fluorescence images exhibit a signal-to-noise ratio (SNR) of about 34 at clinical working distances of 20 mm (distance between tip of endoscope and tissue surface), which is superior to that obtained using the UV Module/CID detector, which has a SNR of about 18 at the same distance. The use of the CCD eliminates the need for the optics module and greatly simplifies system design. In addition, it also avoids problems associated with the tendency of the UV module to rotate in the biopsy channel. By using the same detector and optics for white light and fluorescence images, perfect registration of these two images can be obtained. Parallax between the white light image of the CCD and the fluorescence image of the optics module was a significant problem. The CCD in this particular embodiment contains 88,560 pixels compared to 10,000 fibers for the UV module, resulting in higher total image resolution. The objective lens on the Pentax colonoscope has better imaging properties than the UV module. The characteristic width for the line spread function of the lens of this embodiment is 200 mm compared to 400 mm for the UV Module. The overall rigidity of the spectral endoscope is not increased significantly with a single UV illumination fiber.
The diagnostic methods employed can be based on the overall fluorescence intensity difference between normal mucosa and dysplasia. Thus, in certain applications it is preferable to collect the fluorescence emission over the full band between 400-700 nm. However, accurate measurements can use a point contact device such that diagnostic information can be obtained by sampling the fluorescence at a plurality of specific wavelengths such as 460, 600 and 680 nm, for example. For many applications the preferred range for fluorescence excitation is between 350 nm and 420 nm.Endoscopic imaging studies with the electronic CCD endoscope can include the use of color CCD""s, which have the ability provide such information.